The relationship between serum metabolites and cellular immune function in children with sepsis
Objective To investigate the relationship between serum metabolites and cellular im-mune function in children with sepsis.Methods A total of 33 children with sepsis admitted to our hospital from April 2021 to 2024 April were selected as research group,and healthy children of the same age as the subjects were selected as control group.The subjects were collected in the morning and venous blood was drawn.Metabolomics was used to analyze the changes in sugar metabolism-related metabolites in the serum of the two groups of recruited subjects.Peripheral blood mononuclear cells were separated,and the propor-tion of CD3+,CD4+,CD8+,CD4+/CD8+T lymphocytes and Treg cells was detected by flow cytometry.The expression levels of programmed cell death protein 1(PD-1),cytotoxic T lymphocyte-associated anti-gen-4(CTLA-4),B and T lymphocyte attenuator(BTLA),and T cell immunoglobulin mucin-3(Tim-3)were analyzed by quantitative polymerase chain reaction(PCR).The relationship between metabolite chan-ges and CD4+/CD8+T lymphocytes and Treg cells was analyzed by correlation analysis.The relationship between metabolite changes and PD-1,CTLA-4,BTLA,and Tim-3 expression levels was analyzed.Between-group quantitative data were compared by t-test.Results Metabolomics found that serum sedo-heptulose and 2-deoxyd-galactose were significantly increased in patients with sepsis.Therefore,sedohep-tulose and 2-deoxyd-galactose were selected as research objects in this study.The relative levels of sedo-heptulose and 2-deoxyd-galactose in serum of control group(0.98±0.07,0.99±0.08)were significantly lower than those in patients with research group(1.77±0.18,1.58±0.16,t=23.150,18.960,P＜0.05).CD3+T lymphocytes,CD4+T lymphocytes,CD8+T lymphocytes,CD4+/CD8 T lymphocytes ratio[(55.61±3.74)％,(53.45±3.90)％,(31.43±3.09)％,1.93±0.11]in control group was signifi-cantly higher than that in patients with research group(47.00±4.51)％,(42.89±4.61)％,(23.71±3.02)％,1.34±0.13,t=8.434,10.040,10.270,19.350,P＜0.05].Treg cells in control group[(2.04±0.29)％]significantly lower than that in patients with research group[(4.45±0.72)％,t=17.840,P＜0.05].The mRNA expression levels of PD-1,CTLA-4,BTLA and Tim-3 in blood immune cells of control group(0.96±0.07,0.91±0.08,0.80±0.12,0.71±0.14)was significantly lower than that in patients with research group(1.75±0.14,1.56±0.19,1.41±0.12,1.45±0.16,t=30.230,18.410,20.340,19.870,P＜0.05).The relationship between serum metabolites and cellular immune function in sepsis children The serum levels of sedoheptulose and 2-deoxy-D-galactose in sepsis patients were negatively correlated with CD3+T lymphocytes,CD4+T lymphocytes,CD8+T lymphocytes,and the ratio of CD4+/CD8+T lymphocytes(r=-0.514,-0.631,-0.354,-0.478,P＜0.05;r=-0.401,-0.522,-0.308,-0.417,P＜0.05).The serum levels of sedoheptulose and 2-deoxy-D-galactose were positively correlated with the proportion of Treg cells(r=0.265,0.358,P＜0.05).The serum levels of sedoheptulose and 2-deoxy-D-galactose were positively correlated with the expression levels of PD-1,CTLA-4,BTLA,and Tim-3 mRNA(r=0.214,0.321,0.411,0.202,P＜0.05;r=0.300,0.216,0.308,0.415,P＜0.05).Conclusion The serum levels of sedoheptulose and 2-deoxy-D-galac-tose in sepsis patients are significantly increased,inversely related to the CD4+/CD8+T lymphocyte ratio,positively related to the proportion of Treg cells,and associated with T cell exhaustion.
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